tbuckley/cabot-search huggingface dataset:
Choosing Wisely Africa: Insights from the front-lines of clinical care.
Authors: Fidel Rubagumya, Kevin Makori, Hirondina Borges, Sitna Ali Mwanzi, Safiya Karim, Susan Citonje Msadabwe, Nazima Jaffer Dharsee, Miriam Claire Mutebi, Wilma M. Hopman, Verna D. Vanderpuye, Sidy Ka, Ntokozo Ndlovu, Nazik Hammad, Christopher M. Booth
Journal: Journal of Clinical Oncology (2022)

e18835 Background: A multidisciplinary Task Force of African oncologists and patient representatives published the Choosing Wisely Africa (CWA) recommendations in 2020. These recommendations identified low-value, unnecessary, or harmful practices that are frequently used in Sub-Saharan Africa (SSA). We describe agreement and concordance with the recommendations from front-line oncologists across SSA. Methods: A self-administered electronic survey was distributed to members of the African Organization for Research &amp; Training in Cancer and oncology groups within SSA using a hierarchical snowball method. The survey captured information about awareness of CWA, agreement with recommendations, and concordance with clinical practice. Descriptive statistics were used to summarize study results. Results: 49 individuals responded to the survey; 61% (30/49) were female and 59% (29/49) were clinical oncologists. Respondents represented 14 countries in SSA; 69% (34/49) practiced exclusively in the public system. Only 43% (21/49) were aware of the CWA list and 90% (44/49) agreed it would be helpful if the list was displayed in their clinic. There was generally high agreement (Table) with the recommendations (range 84-98%); highest agreement related to staging/defining treatment intent (98%). The proportion of oncologists who implemented these recommendations in routine practice was somewhat lower (range 68-100%). Lowest rates of concordance related to: use of shorter schedules of radiotherapy (68%). Conclusions: While most frontline SSA oncologists agree with CWA recommendations, efforts are needed to disseminate the list. Agreement with the recommendations is high but there are gaps in implementation in routine practice. Further work is required to understand barriers and enablers of implementation.[Table: see text]
Three-dimensional digital models in kidney cancer surgery: Results and video-illustrated technique of an institutional series
Authors: F. Lavagno, A. Vignola, M. De Bellis, F. Vitiello, D. D’agate, G. Calleris, P. Destefanis, F. Soria, M. Allasia, P. Gontero
Journal: European Urology (2022)
Solid Fuel, Secondhand Smoke, and Lung Cancer Mortality: A Prospective Cohort of 323,794 Chinese Never-Smokers
Authors: Elvin S. Cheng, Ka Hung Chan, Marianne Weber, Julia Steinberg, Jane Young, Karen Canfell, Xue Qin Yu
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Household air pollution and secondhand tobacco smoke are known carcinogens for lung cancer, but large-scale estimates of the relationship with lung cancer mortality are lacking.
CXCR4+ Treg cells control serum IgM levels and natural IgM autoantibody production by B-1 cells in the bone marrow
Authors: Shlomo Elias, Rahul Sharma, Michael Schizas, Izabella Valdez, Sham Rampersaud, Sun-Mi Park, Paula Gonzalez-Figueroa, Quan-Zhen Li, Beatrice Hoyos, Alexander Y. Rudensky
Journal: The Journal of Experimental Medicine (2022)

Regulatory T (Treg) cells represent a specialized lineage of suppressive CD4+ T cells whose functionality is critically dependent on their ability to migrate to and dwell in the proximity of cells they control. Here we show that continuous expression of the chemokine receptor CXCR4 in Treg cells is required for their ability to accumulate in the bone marrow (BM). Induced CXCR4 ablation in Treg cells led to their rapid depletion and consequent increase in mature B cells, foremost the B-1 subset, observed exclusively in the BM without detectable changes in plasma cells or hematopoietic stem cells or any signs of systemic or local immune activation elsewhere. Dysregulation of BM B-1 B cells was associated with a highly specific increase in IgM autoantibodies and total serum IgM levels. Thus, Treg cells control autoreactive B-1 B cells in a CXCR4-dependent manner. These findings have significant implications for understanding the regulation of B cell autoreactivity and malignancies.
HDAC inhibitor Tucidinostat plus exemestane as neoadjuvant therapy in patients with hormone receptor positive, HER2 negative breast cancer.
Authors: Xin Wang
Journal: Journal of Clinical Oncology (2022)

e12623 Background: Tucidinostat (formerly known as chidamide) is an oral subtype-selective histone deacetylase (HDAC) inhibitor with demonstrated efficacy and safety in combination with exemestane in postmenopausal patients with advanced, hormone receptor-positive breast cancer. The aim of this study was to evaluate the efficacy of tucidinostat combined with exemestane as neoadjuvant strategy in hormone receptor-positive early breast cancer patients. Methods: The study (ChiCTR2100046678) is a single-center, prospective, open-labeled, single-arm phase II study. Patients with HR-positive, HER2-negative, and node-positive, stage II–III breast cancer were enrolled at Tianjin Medical University Cancer Institute and Hospital. Eligible patients received 30 mg oral tucidinostat twice weekly in combination with 25 mg oral exemestane daily for up to a total of 24 weeks. The primary endpoint was to determine percent of pts who achieve a PEPI score of 0. The secondary endpoints were to analyze the the pathological complete remission (pCR) rate, complete cell cycle arrest (CCCA, defined as Ki67&lt;2.7%), objective response rate (ORR), disease control rate (DCR) and event free survival (EFS), and overall survival (OS) as well as the safety and tolerability. Results: Patient enrollment initiated in Jan. 2021 and ended in Nov. 2021. Of the 20 pts enrolled, 20 were treated and radiologically evaluable for response. The ORR was 40% with CR 5% (n=1) and PR 35% (n=7). The DCR was 100%. Four patients were still on wait lists for surgery. Of the 16 pts with surgery, one case achieved pCR. The follow-up remains ongoing and updated results will be presented thereafter. Most adverse events (AEs) were grade 1 or 2. Grade 3 AEs included neutropenia (11.8%), thrombocytopenia (5.9%) and lung infection (5.9%), respectively. Conclusions: The combination of Tucidinostat and exemestane was well tolerated with encouraging clinical responses in early hormone receptor positive, HER2 negative breast cancer. Further investigation is warranted. Clinical trial information: ChiCTR2100046678.
National organization addresses multidisciplinary oncology team burnout and resiliency through multifaceted presidential theme education initiative.
Authors: Leigh Boehmer, Krista Nelson, Lorna Lucas, Lisa Townsend, Lori Gardner, Monique Marino
Journal: Journal of Clinical Oncology (2022)

e23017 Background: The 2021-2022 Association of Community Cancer Centers (ACCC) President’s Theme centered on strengthening a work culture that supports professional well-being and workforce resilience. To support this theme and help ensure sustainable high quality cancer care delivery, ACCC —an education and advocacy organization for the multidisciplinary oncology care team (MDT)—designed a multifaceted professional development initiative. Educational interventions were designed to address team member burnout and building resilience, critical issues facing members of today’s oncology workforce. Methods: ACCC designed a collaborative and bi-directional peer-support educational initiative to drive the mission of the 2021-2022 ACCC President’s Theme. Professional Development opportunities included: 1) Expert-led mindfulness meditation series of 10 guided exercises tailored to help MDT members manage through social, emotional, physical, and mental health challenges. 2) Professional development themed virtual meetings, styled as “Coffee Chat Learning Sessions,” facilitated by the ACCC President, addressing emergent challenges and opportunities facing MDT members. 3) Podcast series featuring timely topics related to MDT well-being and resiliency amid the COVID-19 Pandemic. Podcast topics include a) The Business Case for Hiring Oncology Social Workers. b) Leading with Gratitude. c) Coping with Pandemic Grief. d) A Summer of Disconnect for Cancer Professionals. e) COVID-19 Self-Care. f) Real-World Lessons from COVID-19. Results: The education initiative reached a diverse cohort of oncology care community members. 76 unique professionals participated in the small group “Coffee Chat Learning Sessions” from 25 states and represented 72 unique cancer care programs, practices, and institutions. The meditation series engaged more than 1,100 users and the podcast series garnered 1,870 learners. The podcast episode titled “COVID-19 Self Care” was the third most accessed ACCC Podcast episode of all time with more than 680 views. Over 2,900 learners accessed and engaged with the ACCC President’s Theme resources across the dedicated webpage from March 2021-January 2022. Conclusions: Anecdotal learner feedback has been overwhelmingly positive regarding this professional development educational initiative. In a climate of high burnout and health care worker fatigue, the ACCC 2021-2022 President’s Theme Education program has served as a unique lifeline and resource to members of the oncology community to restore and develop resiliency, enhance well-being, and advance professional connections and peer-to-peer support to meet continued challenges. Lessons learned from these activities will guide and inform future professional development opportunities.
A study of neoadjuvant sintilimab combined with chemotherapy TP for locally advanced esophageal squamous cell carcinoma (ESCC).
Authors: Zhao Li, Peng-Fei Xu, Wei-Min Mao, YuKang Kuang, Hai-Yin Fan, Bin Zou, Jian-Feng Zhu, Chao Li, Xiao-Liang Cheng, Xing-Fei Liu, Changying Guo
Journal: Journal of Clinical Oncology (2022)

e16038 Background: Although preoperative chemoradiotherapy is the standard of care for patients with locally advanced esophageal cancer, ESCC still has a dismal prognosis. Sintilimab, a humanized IgG4 monoclonal antibody with high affinity and specificity for PD-1, has shown promising efficacy with overall survival in ESCC in a phase II study (ORIENT-02, NCT03116152) 1 . KEEP-G 03 given the encouraging MPR and favorable tolerability of preoperative sintilimab in combination with triplet chemotherapy in resectable ESCC (KEEP-G 03, NCT03946969) 2 . This trial evaluates the feasibility and safety of preoperative sintilimab in combination with chemotherapy of TP in ESCC. Methods: This is a single-arm, single center research, phase 2 trial to assessment the efficacy and safety of a sintilimab and chemotherapy of TP(Q3W 2-4 cycle) as neoadjuvant treatment of locally advanced ESCC. The key eligibility criteria was locally advanced ESCC, ECOG PS 0 or 1, and at least one measurable lesion per RESIST v1.1. a Sintilimab: 200mg for 60kg, 3mg/kg for body weight &lt; 60kg; TP: pacilitaxel 175mg/m 2 plus cisplatin 75mg/m 2 . Primary Objectives: pCR, MPR. Secondary Objectives: R0 rate, RFS, OS, Safety (CTCAE 5.0). Exploratory Objectives: The alteration of molecular biomarkers to neoadjuvant treatment including PD-L1, TMB, DDR, etc. Results: From 1/2020 to 12/2021, 20 eligible patients were recruited in the Jiangxi Tumor Hospital, NanChang, China. Conclusions: Given the encouraging MPR and favorable tolerability, the combination of sintilimab and chemotherapy of TP could be a potentially feasible and safe neoadjuvant option for locally advanced ESCC. The trial will be continued to evaluate the feasibility of this regimen.[Table: see text][Table: see text][Table: see text]
Implication of Orai1 in the diastolic calcium dysregulation during Ischemia and Reperfusion in cardiomyocytes
Authors: D Falcon Boyano, I Mayoral Gonzalez, E Calderon Sanchez, A Ordonez, T Smani
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Agencia Estatal de Investigación Background It is well established that abnormalities in the regulation of the intracellular concentration of Ca2+ ([Ca2+]i) occurrs in diseased heart. Ischemia/Reperfusion (I/R) syndrome is characterized by [Ca2+]i overload that might be associated with the increase of left ventricular pressure, which might trigger diastolic dysfunction. Several studies have demonstrated that Orai1/2/3 isoforms of the Store Operated Calcium Channels (SOCC) and TRPC channels play a role in cardiac pathologies. Previously, we demonstrated that the expression of Orai1 increased after I/R although their role in the diastolic [Ca2+]i regulation is unknown. Objective The aim of this study was to examine the role of SOCC in the diastolic [Ca2+] after I/R in cardiomyocytes and the activation of transcription factors by I/R. Materials and Methods The experiments were performed in adult (ARVM) and neonatal rat ventricular cardiomyocytes (NRVM) and in a rat model of myocardial I/R. Ca2+ studies were realized using microfluorimetric technique in FURA-2AM loaded cardiomyocytes. To evoke [Ca2+]i transients, ARVM were field stimulated at 0.5Hz and NRVMs at 1Hz. Immunofluorescence was used to investigated CREB activation using a specific phospho-CREB antibody and protein expression was analysed by Western Blot. Orai1 expression was assessed in rat samples and in ventricular biopsies of patients with ischemic heart failure. Results We found that field stimulation of ARVM from I/R animal showed significant increase in the diastolic [Ca2+]i as compare to AVRM isolated from sham rats. Also, NRVM subjected to simulated protocol of I/R presented similar increase in the diastolic [Ca2+]i. These responses correlated with significant increase in the expression of Orai1 in both cardiomyocytes. Interestingly, NRVM and ARVM preincubation with SYNTA-66 and GSK-7975A to block SOCC successfully reduced the increase in the diastolic [Ca2+]I induced by IR. Moreover, we found that I/R promoted CREB activation through PKA activation, but not though EPAC2 or ERK1/2. Finally, we found that Orai1 is overexpressed in ventricle biopsies of patient with heart failure from ischemic origin. Conclusions Our results confirms that I/R induced an upregulation of Orai1 which was associated with diastolic dysfunction, suggesting that Orai1 plays a role in the I/R induced diastolic [Ca2+]i increase. Moreover, our data demonstrated the activation of the transcription factor CREB in cardiomyocytes after I/R, known to activate a plethora of genes involved in the adverse cardiac remodelling.
Continence after introducing NeuroSAFE in radical prostatectomy
Authors: M.A. van der Slot, S. Remmers, G.J.L.H Van Leenders, D. Muijlaert, M.B. Busstra, M. Gan, O.S. Klaver, J.B.W. Rietbergen, M.A. Den Bakker, C.F. Kweldam, C.H. Bangma, M.J. Roobol, L.D.F Venderbos
Journal: European Urology (2022)
Correlation of BRAF genomic alterations with higher mutation burden and predictive response to immune checkpoint inhibitors among human malignancies.
Authors: Feng-Che Kuan, Chung-Sheng Shi, Meng-Hung Lin
Journal: Journal of Clinical Oncology (2022)

e14589 Background: The treatment of BRAF-mutated melanoma leads the evolution of management in BRAF-mutated human malignancies from targeted agents to immune checkpoint inhibition. The correlation between BRAF genomic alterations and mutation burden is not well-studied as well as its prognostic role and predictive role to immune checkpoint inhibitors. Methods: Three Public genomic database (AACR GENIE v.11 [N = 119,058], MSKCC pan-cancer [10,080], MSKCC ICI [1,608]) were retrieved from cBioPortal ( https://www.cbioportal.org ). Raw data of cancer types, BRAF status, mutation counts (MC), exposure to immune checkpoints inhibitors (ICIs), and survival were analyzed. Violin plots were used to compare the distribution of MC among BRAF-altered and -wild tumors, and the Kaplan-Meier method was used to estimate survival rates. Statistical significance was set at a two-sided P &lt; 0.05. Results: BRAF genomic alterations exist in 7,361 (6.2%, AACR GENIE v.11), 560 (5.6%, MSKCC pan-cancer) and 165 patients (10.3%, MSKCC ICI). There are 4,851 (4.1%), 357 (3.6%), and 312 (19.4%) patients with melanoma in these database, respectively. AACR GENIE v.11 includes the other two MSKCC databases, and 10.7% (N = 1,074) patients in MSKCC pan-cancer databases are also cases in MSKCC ICI. The median MCs were 7/Mb and 4/Mb, with interquartile ranges of 1 to 1,467 and 1 to 821 in the BRAF-altered and -wild tumors in AACR GENIE v.11. In this three databases, the distribution of MC was different between the BRAF-altered and -wild tumors (p &lt; 0.001). In MSKCC pan-cancer cohort, the median overall survival in BRAF-altered and -wild tumors are 22.8 vs. 26.3 months (logrank p = 0.005). In MSKCC ICI cohort, the median overall survival of BRAF-altered and -wild tumors are 47.0 vs. 17.0 months (logrank p &lt; 0.001). Conclusions: BRAF genomic alterations are associated with higher mutation counts, represent a poor prognostic factor and positively predictive to immune checkpoint inhibition among human malignancies.
A randomized phase III clinical trial of yoga for chemotherapy-induced peripheral neuropathy treatment.
Authors: Katherine Han, Andee Dooley, Lauren Piulson, Christina Seluzicki, Wanqing Iris Zhi, Ting Bao
Journal: Journal of Clinical Oncology (2022)

TPS12146 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, painful, and debilitating side effect of many standard chemotherapy regimens. Patients with CIPN typically experience pain, paresthesia, and muscle weakness, and may exhibit significant functional decline and worsened quality of life. Our prior study showed more than half of breast cancer survivors experience persistent CIPN up to a mean duration of 5.6 years, which is associated with a doubled fall risk. Identifying nonpharmacological approaches to reduce CIPN symptoms and improve cancer survivors’ outcomes is urgently needed. Yoga is a meditative movement therapy that that includes stretching, and flexibility and balance training. Our pilot study (NCT03292328) demonstrated that yoga reduced CIPN-related symptoms, and improved quality of life and functional reach scores compared to waitlist control. We hypothesize that yoga can reduce CIPN symptoms, improve function, and reduce the risk of falls. Methods: We are conducting a three-arm randomized education and usual care-controlled trial in cancer survivors with chronic CIPN pain at Memorial Sloan Kettering Cancer Center (MSK), New York, NY. Participants in the intervention arm will receive twice-weekly one-hour Hatha yoga classes virtually or in-person taught by MSK instructors, and practice yoga at home daily for eight weeks. Participants in the education control arm will receive one-hour virtual education classes twice per week taught by an MSK mind-body therapist for eight weeks. Participants in the usual care arm will continue their usual care for CIPN for eight weeks. The primary endpoint is the Brief Pain Inventory-Short Form (BPI-SF) average pain item at weeks 8 and 24. Secondary outcomes include the Neuropathic Pain Scale (NPS), Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health outcome measure, Brief Fatigue Inventory (BFI), Insomnia Severity Index (ISI), Hospital Anxiety and Depression Scale (HADS), QLQ-CIPN-20, Functional Assessments, and quantitative sensory testing (QST) at weeks 0, 4, 8, 12, 18, and 24. Eligibility criteria included: 1) Moderate-to-severe CIPN pain, defined by a score of 4 or greater on a 0-10 numerical rating scale; 2) completion of neurotoxic chemotherapy at least three months prior; 3) no changes in anti-neuropathy medications within three months of enrollment; and 4) changes in balance and functionality. We have accrued five participants as of February 2022 with a total accrual target of 268 participants. We anticipate completing accrual in March 2025. Funding resource: NIH R01CA251470. Clinical trial information: NCT05121558.
QOL-28. Clinico-molecular correlates of quality of survival and neurocognitive outcomes in medulloblastoma; a meta-analysis of the SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 trials
Authors: Mathilde Chevignard*, Kim S Bull*, James Holt, Bertie Harrington, Jemma Castle, Marie-Amelie Heng, Colin Kennedy, Francois Doz, Birgitta Lannering, Stefan Rutkowski, Maura Massimino, Simon Bailey, Adeoye Oyefiade, Donald Mabbott, Steven C Clifford†, Debbie Hicks†
Journal: Neuro-Oncology (2022)

Abstract Determinants of survivorship outcomes are emerging from limited studies of medulloblastoma (MB) survivors. We undertook an integrated analysis of biological (tumour group, host genetics) and clinico-demographic features in patients treated on the SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 clinical trials with available quality of survival (QoS) data (n=218), to determine key correlates of survivorship, and their clinical potential. Treatment/demographic factors and molecular subgroup (MBWNT, MBSHH, MBGrp3, MBGrp4) were assessed against health status, behavioural functioning, and health-related quality of life (HrQoL). In DNA from HIT-SIOP-PNET4 (n=74), 39 candidate SNPs with known modifying effects on neurocognitive outcomes (e.g., involved in oxidative stress/inflammation) were genotyped and assessed against Wechsler Intelligence Scale (WISC) scores. As expected, MBSHH was associated with improved HrQoL, but subgroup did not associate further with QoS outcomes. SIOP-UKCCSG-PNET3 patients receiving chemotherapy before craniospinal irradiation (CSI) had significantly lower health status (p=0.021) and behavioural functioning (p&amp;lt;0.016) compared to patients treated with CSI alone, and those treated on both arms (maintenance chemotherapy and hyperfractionated (36Gy) or standard (23.4Gy) CSI) of HIT-SIOP-PNET4. SIOP-UKCCSG-PNET3 patients receiving CSI-only had better HrQoL scores than those who received pre-CSI chemotherapy and both HIT-SIOP-PNET4 arms (p=0.004). Females reported worse HrQoL/behavioural functioning across both trials (p&amp;lt;0.04). In HIT-SIOP-PNET4, longer intervals from diagnosis to CSI predicted worse HrQoL/health status (p&amp;lt;0.05). Neither molecular group nor clinico-demographic features tested were associated with neurocognition. In contrast, 6 SNPs significantly associated with ≥1 WISC domain; 4/6 showed multiple associations and were independently prognostic; further associations were apparent at the gene/pathway level. This large, integrated and multi-disciplinary analysis of two independent trials cohorts has revealed multiple factors predictive of medulloblastoma survivorship including treatment (chemotherapy, time to CSI), tumour (molecular group) and host genetic factors. Assessment in further prospective series are required to determine their potential as a basis for modifications to disease management.
Fluorine-18 (18F) Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) and the diagnosis and staging of primary Prostate Cancer (PCa)
Authors: M.H.V. Byrne, N. Ranasinha, C. Mercader, M. Raslan, F. Lewis, S. Gorgoraptis, G. Sathanapally, A.C. Lopes Vieira, J. Golebka, B. Peiris, M. Tuthill, A. Protheroe, P. Camilleri, P. Turner, G. Andrade, S. Miah, T. Leslie, R. Bryant, F. Hamdy, R. Macpherson, F. Gleeson, F. Lopez, A.D. Lamb
Journal: European Urology (2022)